Beichu Guo, PhD

Research Interests Dr. Guo received his Ph.D. in Immunology from the University of Washington, under the supervision of Dr. David Rawlings, where Dr. Guo studied the proximal signaling complex of antigen receptors and NF-B activation in B cells. He also elucidated the role of protein kinase C and CARMA1 (CARD11)-mediated NF-B activation in the growth and survival of B cell lymphomas. Then Dr. Guo joined the laboratory of Dr. Genhong Cheng as a postdoctoral fellow at the Department of Microbiology, Immunology and Molecular Genetics, Jonsson Comprehensive Cancer Center, UCLA. From 2008-2010, Dr. Guo was also chosen as a Special Fellow by the Leukemia & Lymphoma Society (LLS). His postdoctoral research was involved in two areas: the innate signaling pathways triggered by bacterial or viral infection, and the role of innate immunity and inflammation in autoimmune diseases. At the end of 2010, Dr. Guo became an independent investigator at the Department of Microbiology & Immunology, Hollings Cancer Center, Medical University of South Carolina (MUSC). Research in the Guo laboratory is focused on the role of innate immune system, especially inflammasomes, in autoimmune diseases and cancer. Recently, Dr. Guo has been awarded an American Cancer Society (ACS) Research Scholar Grant for his research on senescence-associated inflammation and cancer progression.

Inflammasomes in tumor microenvironment and cancer metastasis Although genetic alternations are critical for cellular transformation and tumor development, emerging evidence indicates that tumor microenvironments exert a significant impact on tumor progression. We are studying the role of inflammasome pathways in tumor microenvironments during cancer initiation, growth and metastasis. We also investigate how inflammasomes contribute to inflammatory and immunosuppressive microenvironments that affect host anti-tumor immunity and conventional cancer therapies.

Senescence-associated inflammation in tumor immunity and tumor progression I am particularly interested in the immune response during early stages of tumor development such as oncogenic transformation and oncogene-induced senescence. In response to oncogene activation or DNA damage, cells can enter a state of growth arrest, referred to as cellular senescence. In addition, chemotherapies, and even anti-tumor immune response can induce senescence in normal or tumor cells. Traditionally, cellular senescence has been defined as a barrier against malignant transformation. Paradoxically, recent progress indicates that senescence also has pro-oncogenesis properties. Therefore, understanding the mechanisms regulating tumor-promoting vs. -inhibiting effects of senescence will provide potential strategies for cancer therapies. We will investigate how the crosstalk between senescent cells and innate immune cells influences senescence, SASP and tumor development. Furthermore, our study will also directly address a key question about the origin of tumor-associated inflammation.

Innate pathways and Inflammasomes in autoimmune diseases Our laboratory is also interested in understanding the role of innate immune system, including Toll-Like Receptors (TLRs), interferon pathways and inflammasomes in autoimmune diseases, such as inflammatory bowel diseases (IBD) and multiple sclerosis. Our previous studies revealed a novel immunoregulatory function of TLR-mediated interferon pathways on the innate and antigen-specific immune response. The aim of our current research is to elucidate the mechanisms for the therapeutic efficacy of type I interferon in the treatment of certain cancer and autoimmune diseases. Our recent studies demonstrate that chronic inflammasome activation promotes the development of intestinal inflammation. The aims of this project are to identify downstream mediators of inflammasome/IL-1 in chronic colitis, and to delineate the role of various inflammasomes in the complex interaction of gut epithelial cells, immune cells and microbiota during intestinal inflammation and tumorigenesis.